63 articles - From Friday Jul 22 2022 to Friday Jul 29 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Haematologica |
Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel. e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The issued recommendations may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM candidates to active treatment. |
meta-analyses and systematic reviews
| Blood Adv |
Interventions to reduce infections in patients with hematological malignancies: a systematic review and meta-analysis. Findings should be interpreted with caution given high risk of bias in many studies. There is a clear need for high-quality contemporary trials to establish the effectiveness of different approaches to prevent infections. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
SARS-CoV-2 humoral responses following booster BNT162b2 vaccination in patients with B-cell malignancies. No significant between group differences were observed. Patients with B-cell malignancies have inferior humoral responses against SARS-CoV-2 and booster dose enhances the NAb response in a proportion of these patients. |
| Ann Oncol |
Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASG12D mutated non-small cell lung cancer. KRAS G12D lung cancers harbor distinct clinical, genomic, and immunologic features compared to other KRAS mutated lung cancers and worse outcomes to PD-(L)1 blockade. Drug development for KRAS G12D lung cancers will have to take these differences into account. |
| Blood |
Avapritinib for Advanced Systemic Mastocytosis. The phase I EXPLORER and phase II PATHFINDER trials demonstrated that avapritinib can elicit complete and durable clinical responses, and molecular remission of KIT D816V. Key management challenges relate to the complex mutational landscape of AdvSM, often found with an associated hematologic neoplasm. |
Erythroblastic islands foster granulopoiesis in parallel to terminal erythropoiesis. Finally, by molecular profiling, we reveal the heterogeneity of EBI macrophages by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo and provide a searchable, online viewer of this data characterizing the macrophage subsets serving as hematopoietic niches. Taken together, our findings demonstrate that EBIs serve a dual role as niches for terminal erythropoiesis and granulopoiesis and the central macrophages adapt to optimize production of red blood cells or neutrophils. |
Gab2-MALT1 Axis Regulates Thromboinflammation and Deep Vein Thrombosis. Overall, our data reveal a previously unrecognized role of the Gab2-MALT1 axis in thromboinflammation. Targeting the Gab2-MALT1 axis with MALT1 inhibitors may become an effective strategy to treat DVT by suppressing thromboinflammation without inducing bleeding complications. |
Loss of sphingosine kinase 2 promotes the expansion of hematopoietic stem cells by improving their metabolic fitness. Deletion of Sphk2 increases hypoxic responses by stabilizing the HIF1a protein to upregulate PDK3, a glycolysis checkpoint protein for HSC quiescence, which subsequently enhances the function of HSCs by improving their metabolic fitness; specifically, it enhances anaerobic glycolysis but suppresses mitochondrial oxidative phosphorylation and generation of reactive oxygen species. Overall, targeting Sphk2 to enhance the metabolic fitness of HSCs is a promising strategy to expand and rejuvenate functional HSCs. |
Prophylactic administration of HPA-1a-specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice. HPA-1a-negative female mice treated prophylactically with anti-HPA-1a antibody prior to exposure to HPA-1a-positive platelets gave birth to HPA-1a-positive pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish both the potential and threshold exposure targets for prophylactic treatment with HPA-1a-specific antibodies for the prevention of FNAIT in humans. |
Proteomic and Phosphoproteomic Landscapes of Acute Myeloid Leukemia. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis. |
T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. Our data demonstrate the relevance of T-cell exhaustion in bispecific antibody therapy and highlight that T cells can be functionally and transcriptionally rejuvenated with TFIs. In view of the growing number of bispecific molecules being evaluated in clinical trials, our findings emphasize the need to consider and evaluate TFIs in application schedules to improve clinical outcomes. |
The Role of Allogeneic Transplant for Adult Ph+ ALL in CR1 with Complete Molecular Remission: A Retrospective Analysis. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints. In conclusion, adult patients with Ph+ ALL who achieved CMR within 90 days of starting treatment did not derive a survival benefit from allo-HCT in CR1 in this retrospective study. |
| Blood Adv |
Cerebral vascular injury in transplant-associated thrombotic microangiopathy. In summary, our study confirms that TA-TMA involves the brains of recipients of HCT and is associated with an increased incidence of neurologic symptoms. Based on these findings, we propose that patients with low- or moderate-risk TA-TMA who develop neurologic complications should be considered for TA-TMA-directed therapy. |
Development and performance of a hereditary hemorrhagic telangiectasia-specific quality-of-life instrument. The HHT-QoL score correlated negatively with PROMIS Discretionary Social Activities (r = -0.65) and Social Roles (r = -0.68) and positively correlated with PROMIS Emotional Distress (r = 0.51). In conclusion, the 4-item HHT-QoL instrument provides valuable insight and may be a useful addition to future clinical research in HHT. |
Doxorubicin Pharmacokinetics and Toxicity in Patients with Aggressive Lymphoma and Hepatic Impairment. Although toxicity was greater on cycle 1, the adverse effects were managed safely. These results show that empiric dose reductions of continuous infusion doxorubicin may not be necessary in patients with elevated bilirubin. |
Gender and Early-career Faculty Disparities in Hematology and Oncology Board Review Lecture Series. A positive trend in the participation of women was found at al board review conferences across the studied period. Our data suggest that women and early-career faculty participation in hematology and oncology board review series is inadequate. |
Genetic and immunohistochemical profiling of NK/T-cell Lymphomas reveals prognostically relevant BCOR-MYC association. In conclusion, activating STAT3 mutations are common in ENKTLs and are associated with increased CD30 expression. MYC overexpression is, at least in part, associated with deleterious BCOR mutations, and this BCOR-MYC linkage may have prognostic significance, underscoring the potential utility of immunohistochemistry for MYC in risk stratification of patients with ENKTL. |
Improving NK Cell Function in Multiple Myeloma with NKTR-255, a Novel Polymer-Conjugated Human IL-15. Finally, we observed that combination of NKTR-255 with the anti-CD38 antibody, daratumumab, was effective against MM cells in vitro and in vivo. Taken together, our data suggest a significant impact of NKTR-255 in inducing NK cell function against MM cells with important translational implications. |
Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma. Clinical significance of imaging-guided biopsies of lesions was demonstrated by detection of monoclonal PC in patients without measurable residual disease (MRD) in aspirates from the iliac crest as well as identification of secondary primary malignancies in MRD-negative patients. Furthermore, site-specific clones with different drug susceptibilities and genetically defined high-risk features were detected by our workflow. |
| Haematologica |
Hypercortisolemic Cushing's patients possess a distinct class of hematopoietic progenitor cells leading to erythrocytosis. Collectively, these results indicate that chronic exposure to excess glucocorticoids in vivo leads to erythrocytosis by generating erythroid progenitor cells with a constitutively active GR. Although remission rescues the erythrocytosis and the phenotype of the circulating CD34+ cells, a memory of other prior changes is maintained in remission. |
Improving the anti-acute myeloid leukemia activity of CD123-specific Engager T cells by MyD88 and CD40 costimulation. Our work highlights the need for both toll-like receptor (TLR) pathway activation via MyD88 and provision of costimulation via CD40 to consistently enhance the antitumor activity of CD123. ENG T cells. |
PI3K inhibitors in chronic lymphocytic leukemia: where do we go from here? In addition to these approaches, it is of interest to identify higher-resolution actionable biomarkers that can predict treatment responses and toxicity, and inform personalized treatment decisions. Here, we discuss the current status of PI3K inhibitors in CLL, factors limiting the use of currently approved PI3K inhibitors in CLL, current strategies to overcome these limitations, and where to go next. |
Time spent at home among older adults with acute myeloid leukemia receiving azacitidine- or venetoclax-based regimens. PDH did not differ between therapy groups (adjusted mean, AZA+VEN: 0.68; AZA monotherapy: 0.66; p=0.64) or between disease risk categories (p=0.34). Compared to AZA monotherapy, patients receiving AZA+VEN had longer clinic visits (median minutes: 127.9 vs 112.9, p. |
| J Hematol Oncol |
hUC-EVs-ATO reduce the severity of acute GVHD by resetting inflammatory macrophages toward the M2 phenotype. hUC-EVs-ATO enhanced the alleviation of aGVHD severity in mice compared with ATO and hUC-EVs without weakening GVL activity. hUC-EVs-ATO promoted M1 to M2 polarization via the mTOR-autophagy pathway. hUC-EVs-ATO could be a potential therapeutic approach in aGVHD after allo-HSCT. |
| Lancet Haematol |
Rates of laboratory adverse events by course in paediatric leukaemia ascertained with automated electronic health record extraction: a retrospective cohort study from the Children's Oncology Group. ExtractEHR-based adverse event ascertainment can improve reporting of laboratory adverse events in clinical trials. Funding US National Institutes of Health, St Baldrick's Foundation, and Alex's Lemonade Stand Foundation. |
| Leukemia |
Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), ). |
Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis. Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR |
Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia. Splicing factors and RUNX1 somatic variants were detected exclusively at high-risk evolution; DNMT3A, BCOR/L1 and ASXL1 were present in both. RUNX1, splicing factors and ASXL1 somatic mutations detected at 6 months after IST predicted high-risk evolution. |
| Thromb Haemost |
Current View on the Molecular Mechanisms Underlying Fibrin(ogen)-Dependent Inflammation. This pathway is inhibited by another pathway induced by the interaction of ß15-42 with a putative endothelial receptor. In this review, we briefly describe the previously proposed molecular mechanisms underlying fibrin-dependent inflammation and their advantages/disadvantages and summarize our recent studies of the novel VLDL receptor-dependent pathway of leukocyte transmigration which plays an important role in fibrin-dependent inflammation. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Hypomethylating Agents for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia: Past Discoveries and Future Directions. In this review, we discuss the path to regulatory approval of azacitidine and decitabine, highlighting the substantial efforts that have been made to optimize the dosing schedule and administration of these drugs, including the development of new, oral formulations of both agents. We also review novel combination strategies that are being investigated in ongoing clinical trials for patients with MDS and AML, as well as efforts to expand the current indications of these agents. |
| Blood |
| J Hematol Oncol |
The mitochondrial unfolded protein response (UPRmt): shielding against toxicity to mitochondria in cancer. UPR mt is conserved and activated in cancer in response to mitochondrial stress to maintain mitochondrial integrity and support tumor growth. In this review, we discuss how mitochondria become dysfunctional in cancer and highlight the tumor-promoting functions of key components of the UPR mt . |
| Leukemia |
Immune senescence in multiple myeloma-a role for mitochondrial dysfunction? A link between cellular mitochondrial dysfunction and the acquisition of an abnormal immune phenotype has recently been described and has widespread physiological consequence beyond the impact on the immune system. Here we outline our current understanding of normal immune aging, describe the mechanism of immunometabolic dysfunction in accelerating this process, and propose the role these processes are playing in the pathogenesis of MM. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |